The overall aim of the research program is a more complete understanding of the electrophysiology of the heart, in both normal and arrhythmic states. The immediate goal of the present project is: a) to investigate under voltage clamp the effects of various antiarrhythmic drugs on the ionic currents generating the action potential upstroke and plateau, and b) to determine the possible molecular mechanism of the drug-receptor interaction. Membrane currents will be measured using rabbit Purkinje fibers and a two microelectrode voltage clamp. The relatively simple morphology of the rabbit Purkinje fiber minimizes the problems of non-uniformity in membrane potential and ion concentration associated with most other voltage clamp set-ups. The study will consider the influence of metabolic state and prior activity on the drug effects. The proposed research should increase our fundamental understanding of the electrophysiology of heart muscle, and clarify the therapeutic effects of antiarrhythmic agents and their mode of action on cells of the specialized conducting system in heart.